Over the last two decades, the prevalence of obesity has increased to epidemic proportions in the general population of the US. Gestational diabetes mellitus (GDM) increases the neonate birth weight, which closely associates with the development of adolescent and adult obesity. Therefore, the intrauterine GDM environment predisposes a high risk of obesity in GDM offspring. Our long-term goal is to investigate the underlying mechanisms that increase birth weight and the susceptibility of obesity in GDM offspring. Adiponectin is an adipose-derived hormone and plays an important role in regulating glucose and lipid metabolism. Recent studies revealed that fetal and neonatal serum adiponectin concentrations are 4-7 fold higher than those in adults. Serum adiponectin levels positively correlate with gestational age and body weight, which indicates that adiponectin may regulate fetal development and growth. Furthermore, most recent studies demonstrated that the overexpression of adiponectin promotes obese phenotype in mice, and adiponectin enhances adipocyte differentiation and lipid accumulation. Our preliminary studies demonstrated that newborn mice from mothers with GDM exhibit a high birth weight, elevated adiponectin expression and serum adiponectin protein levels. High fat feeding also induces more weight gain in the GDM offspring. We hypothesize that the GDM intrauterine environment increases fetal adiponectin expression which predisposes high birth weight and susceptibility of obesity in GDM offspring. In Specific Aim 1, we will determine the effect of the GDM intrauterine environment on adiponectin gene expression from fetus to adult using a well established GDM mouse model (db/+). The relationship of maternal or fetal energy metabolism and fetal adiponectin gene expression will be evaluated. In Specific Aim 2, the role of adiponectin in GDM- induced high birth weight and subsequent development of obesity will be studied by cross-mating db/+ and adiponectin gene deficient mice. The results of this project, will not only determine the role of adiponectin in GDM-associated high birth weight and the subsequent development of obesity, but also provide very useful information regarding fetal adiponectin gene expression and the involvement of adiponectin in regulating fetal development and growth under normal gestational condition. These results will lead to a new strategy for obesity prevention. [unreadable] [unreadable] [unreadable]